General anaesthesia reduces the uniqueness of brain connectivity across individuals and across species

The human brain is characterised by idiosyncratic patterns of spontaneous thought, rendering each brain uniquely identifiable from its neural activity. However, deep general anaesthesia suppresses subjective experience. Does it also suppress what makes each brain unique? Here we used functional MRI under the effects of the general anaesthetics sevoflurane and propofol to determine whether anaesthetic-induced unconsciousness diminishes the uniqueness of the human brain: both with respect to the brains of other individuals, and the brains of another species. We report that under anaesthesia individual brains become less self-similar and less distinguishable from each other. Loss of distinctiveness is highly organised: it co-localises with the archetypal sensory-association axis, correlating with genetic and morphometric markers of phylogenetic differences between humans and other primates. This effect is more evident at greater anaesthetic depths, reproducible across sevoflurane and propofol, and reversed upon recovery. Providing convergent evidence, we show that under anaesthesia the functional connectivity of the human brain becomes more similar to the macaque brain. Finally, anaesthesia diminishes the match between spontaneous brain activity and meta-analytic brain patterns aggregated from the NeuroSynth engine. Collectively, the present results reveal that anaesthetised human brains are not only less distinguishable from each other, but also less distinguishable from the brains of other primates, with specifically human-expanded regions being the most affected by anaesthesia.

Entries along the diagonal, represent self-self similarity (correlation of FC patterns), whereas off-diagonal entries represent selfother similarity.(c) Self-self similarity is significantly higher between two conscious states, than between wakefulness and vol 2% sevoflurane.(d) The difference between self-self correlation and mean self-other correlation (differential identifiability) is significantly higher between two conscious states, than between wakefulness and vol 2% sevoflurane.(e) The regional distribution of contributions to identifiability (change in intra-class correlation coefficient) is plotted on the cortical surface.It is significantly spatially correlated with the corresponding map obtained with vol 3% sevoflurane: Spearman ρ = 0.61, pspin < 0.001, N = 200 regions.(f) Identifiability matrix between wakefulness and post-anaesthetic recovery.(g) Identifiability matrix between wakefulness and burst-suppression level of sevoflurane anaesthesia.(h) Self-self similarity is significantly higher between two conscious states, than between wakefulness and burst-suppression level of sevoflurane.(i) The difference between self-self correlation and mean self-other correlation (differential identifiability) is significantly higher between two conscious states, than between wakefulness and burst-suppression level of sevoflurane.(j) The regional distribution of contributions to identifiability (change in intra-class correlation coefficient) is plotted on the cortical surface.It is significantly spatially correlated with the corresponding map obtained with vol 3% sevoflurane: Spearman ρ = 0.80, pspin < 0.001, N = 200 regions.***, p < 0.001.(right).Entries along the diagonal, represent self-self similarity (correlation of FC patterns), whereas off-diagonal entries represent self-other similarity.(c) Self-self similarity is significantly higher between two conscious states, than between wakefulness and propofol anaesthesia.(d) The difference between self-self correlation and mean self-other correlation (differential identifiability) is significantly higher between two conscious states, than between wakefulness and propofol anaesthesia.Box-plot: center line, median; box limits, upper and lower quartiles; whiskers, 1.5× interquartile range.***, p < 0.001.The propofol-induced regional loss of ICC is significantly spatially aligned with the archetypal sensory-association axis of cortical organisation; the regional distribution of inter-individual variability of functional connectivity; the regional distribution of cortical expansion between macaque and human brains; and the regional expression of human-accelerated genes pertaining to brain function and development ("HAR-brain genes"); N = 200 regions

Figure S1 .
Figure S1.Replication of identifiability results at different doses of sevoflurane | (a) Identifiability matrix between wakefulness and post-anaesthetic recovery.(b) Identifiability matrix between wakefulness and vol 2% sevoflurane anaesthesia (right).Entries along the diagonal, represent self-self similarity (correlation of FC patterns), whereas off-diagonal entries represent selfother similarity.(c) Self-self similarity is significantly higher between two conscious states, than between wakefulness and vol 2% sevoflurane.(d) The difference between self-self correlation and mean self-other correlation (differential identifiability) is significantly higher between two conscious states, than between wakefulness and vol 2% sevoflurane.(e) The regional distribution of contributions to identifiability (change in intra-class correlation coefficient) is plotted on the cortical surface.It is significantly spatially correlated with the corresponding map obtained with vol 3% sevoflurane: Spearman ρ = 0.61, pspin < 0.001, N = 200 regions.(f) Identifiability matrix between wakefulness and post-anaesthetic recovery.(g) Identifiability matrix between wakefulness and burst-suppression level of sevoflurane anaesthesia.(h) Self-self similarity is significantly higher between two conscious states, than between wakefulness and burst-suppression level of sevoflurane.(i) The difference between self-self correlation and mean self-other correlation (differential identifiability) is significantly higher between two conscious states, than between wakefulness and burst-suppression level of sevoflurane.(j) The regional distribution of contributions to identifiability (change in intra-class correlation coefficient) is plotted on the cortical surface.It is significantly spatially correlated with the corresponding map obtained with vol 3% sevoflurane: Spearman ρ = 0.80, pspin < 0.001, N = 200 regions.***, p < 0.001.

Figure S3 .
Figure S3.Change in cognitive matching for unimodal versus transmodal ends of the cortical hierarchy|.NeuroSynth maps were correlated with the archetypal axis map of [83]; maps exhibiting a positive correlation were included at the transmodal end, whereas maps correlating negatively were included at the unimodal end.Box-plot: center line, median; box limits, upper and lower quartiles; whiskers, 1.5× interquartile range.***, p < 0.001.

Figure S4 .
Figure S4.Identifiability of individual connectomes is diminished under propofol anaesthesia.(a) Identifiability matrix between wakefulness and post-anaesthetic recovery.(b) Identifiability matrix between wakefulness and propofol anaesthesia (right).Entries along the diagonal, represent self-self similarity (correlation of FC patterns), whereas off-diagonal entries represent self-other similarity.(c) Self-self similarity is significantly higher between two conscious states, than between wakefulness and propofol anaesthesia.(d)The difference between self-self correlation and mean self-other correlation (differential identifiability) is significantly higher between two conscious states, than between wakefulness and propofol anaesthesia.Box-plot: center line, median; box limits, upper and lower quartiles; whiskers, 1.5× interquartile range.***, p < 0.001.

Figure S5 .
Figure S5.Anatomical characterisation of contributions to propofol-induced loss of identifiability | (a) Edge-level difference in intra-class correlation coefficient between awake-recovery and awake-propofol.(b) The anaesthetic-induced loss of ICC is significantly more pronounced for functional connections with an underlying structural direct connection, than without.Box-plot: center line, median; box limits, upper and lower quartiles; whiskers, 1.5× interquartile range.**, p < 0.01.(c) Regional distribution of propofol-induced loss of ICC, projected onto the cortical surface.It is significantly spatially correlated with the corresponding map obtained with sevoflurane: Spearman ρ = 0.35, pspin < 0.001, N = 200 regions.(d)The propofol-induced regional loss of ICC is significantly spatially aligned with the archetypal sensory-association axis of cortical organisation; the regional distribution of inter-individual variability of functional connectivity; the regional distribution of cortical expansion between macaque and human brains; and the regional expression of human-accelerated genes pertaining to brain function and development ("HAR-brain genes"); N = 200 regions

Figure S10 .
Figure S10.Identifiability under anaesthesia is robust to parcellation choice | (a) Identifiability matrix between wakefulness and post-anaesthetic recovery.(b) Identifiability matrix between wakefulness and sevoflurane anaesthesia (right).Entries along the diagonal, represent self-self similarity (correlation of FC patterns), whereas off-diagonal entries represent self-other similarity.(c)Self-self similarity is significantly higher between two conscious states, than between wakefulness and sevoflurane anaesthesia.(d) The difference between self-self correlation and mean self-other correlation (differential identifiability) is significantly higher between two conscious states, than between wakefulness and sevoflurane anaesthesia.(e) The regional distribution of contributions to identifiability (change in intra-class correlation coefficient) is plotted on the cortical surface for the 68 ROIs of the Desikan-Killiany atlas.Box-plot: center line, median; box limits, upper and lower quartiles; whiskers, 1.5× interquartile range.***, p < 0.001.

Figure S11 .
Figure S11.Identifiability under anaesthesia is robust to inclusion of subcortex | (a) Identifiability matrix between wakefulness and post-anaesthetic recovery.(b) Identifiability matrix between wakefulness and sevoflurane anaesthesia (right).Entries along the diagonal, represent self-self similarity (correlation of FC patterns), whereas off-diagonal entries represent self-other similarity.(c) Self-self similarity is significantly higher between two conscious states, than between wakefulness and sevoflurane anaesthesia.(d) The difference between self-self correlation and mean self-other correlation (differential identifiability) is significantly higher between two conscious states, than between wakefulness and sevoflurane anaesthesia.(e) The regional distribution of contributions to identifiability (change in intra-class correlation coefficient) is plotted on the cortical surface for the 200-ROIs of the Schaefer atlas, and plotted in volumetric space for the 32 ROIs of the Tian subcortical atlas.Box-plot: center line, median; box limits, upper and lower quartiles; whiskers, 1.5× interquartile range.***, p < 0.001.

Figure S13 .
Figure S13.Replication of identifiability results upon excluding high-motion individuals | (a) Identifiability matrix between wakefulness and post-anaesthetic recoveryy.(b) Identifiability matrix between wakefulness and sevoflurane anaesthesia.Entries along the diagonal, represent self-self similarity (correlation of FC patterns), whereas off-diagonal entries represent self-other similarity.(c) Self-self similarity is significantly higher between two conscious states, than between wakefulness and sevoflurane.(d) The difference between self-self correlation and mean self-other correlation (differential identifiability) is significantly higher between two conscious states, than between wakefulness and sevoflurane.**, p < 0.01; ***, p < 0.001.(e) The regional distribution of contributions to identifiability (change in intra-class correlation coefficient) is plotted on the cortical surface.It is significantly spatially correlated with the corresponding map obtained when including all individuals: Spearman ρ = 0.94, pspin < 0.001, N = 200 regions.

TABLE S1 .
Statistical results for cognitive matching from NeuroSynth in the sevoflurane dataset.

TABLE S2 .
Statistical results for human-macaque functional similarity in the sevoflurane dataset.

TABLE S3 .
Statistical results for cognitive matching from NeuroSynth in the propofol dataset.

TABLE S4 .
Statistical results for human-macaque functional similarity in the propofol dataset

TABLE S5 .
Statistical results for cognitive matching from NeuroSynth in the sevoflurane dataset, using the Desikan-Killiany anatomical atlas.

TABLE S6 .
Statistical results for BrainMap decoding in the sevoflurane dataset

TABLE S7 .
Statistical results for cognitive matching from NeuroSynth in the sevoflurane dataset, using 200 cortical regions from the Schaefer atlas, and 32 subcortical regions from the Tian atlas.